Hollow fiber membranes made from various materials are widely used as permselective membranes for medical applications such as hemodialysis and blood filtration, as well as for the pharmaceutical industry, food industry, and the like. The hollow fiber membranes used in such applications must have superior mechanical strength and chemical stability, possess easily controllable permeability, release a minimal amount of materials, exhibit almost no interaction with biological components, and be safe for living bodies. However, there have been no hollow fiber membranes completely satisfying all of these requirements.
When the material is a synthetic polymer, for example, the surface is generally hydrophobic. Unduly weak hydrophilic properties tend to cause the material to react with blood components, cause the blood to easily coagulate, and impair the permeability performance of the hollow fiber membrane due to adsorption of protein components. A study for providing the hollow fiber membrane made from such a synthetic polymer with compatibility with blood by incorporating a polymer with hydrophilic properties has been undertaken. For instance, a permselective membrane made from a polysulfone-based polymer with a hydrophilic polymer incorporated therein and a method of manufacturing such a membrane have been proposed. Such a membrane, however, exhibits only poor wetting properties and tends to coagulate blood due to decreased compatibility with blood, if the content of the hydrophilic polymer is small. On the other hand, if the content of the hydrophilic polymer is large, the amount of the hydrophilic polymer dissolved from the membrane increases, although the blood coagulation can be suppressed.
Japanese Patent Applications Laid-open No. S61-238306 and No. S63-97666 disclose a method for preparing a polysulfone-based separation membrane in which a membrane-forming raw material solution contains a polysulfone-based polymer, a hydrophilic polymer, and an additive acting as a non-solvent or a swelling agent on the polysulfone-based polymer. These patents, however, do not describe a method for reducing dissolution of hydrophilic polymers. Japanese Patent Applications Laid-open No. S63-97205, S63-97634, and H04-300636 disclose a method of reducing dissolution of hydrophilic polymers from the polysulfone-based separation membrane prepared by the above method by insolubilizing the hydrophilic polymers by means of a radiation treatment and/or a heat treatment of the membrane. However, this method impair compatibility of the membrane with blood, possibly due to the insolubility of the hydrophilic polymer caused by cross-linking. The membrane obtained by this method contains the hydrophilic polymer in thick membrane areas (inner parts of membrane) as well, precluding the thick membrane areas from exhibiting required hydrophobicity.
Japanese Patent Applications Laid-open No. S61-402 and S62-38205 disclose membranes containing a hydrophilic polymer only in the dense layer side. Japanese Patent Application Laid-open No. H04-300636 discloses a membrane containing polyvinyl pyrrolidone present in a higher concentration in the inner surface side than in other parts of the hollow fiber membrane. There patents, however, only describe that the hydrophilic polymers are present near the surface of the membrane coming into contact with blood, but do not describe any specific properties of the polymers. In addition, no sufficient hydrophobicity can be obtained in the thick membrane areas of these hollow fiber membranes.
Several researches are being undertaken with an objective of providing hollow fiber membranes with superior biological compatibility by modifying the polymers so that the surface has not only hydrophilic properties but also a structure similar to a biomembrane. Specifically, one such research contemplates improvement of biocompatibility of hollow fiber membranes by incorporating a copolymer of 2-methacryloyloxyethyl phosphorylcholine and other monomers having a structure similar to phospholipids, major components forming biomembranes, into synthetic polymer hollow fiber membranes.
Japanese Patent Application Laid-open No. H10-296063 discloses a polysulfone-based porous membrane and a method of manufacturing the same. The porous membrane is produced using a mixed solution of a copolymer of 2-methacryloyloxyethyl phosphorylcholine and other monomers and a polysulfone as a membrane-forming raw material solution. The membrane obtained by this method, however, contains the copolymer of 2-methacryloyloxyethyl phosphorylcholine and other monomers in thick membrane areas (inner parts of membrane) as well, precluding the thick membrane areas from exhibiting hydrophobicity. In addition, the copolymer may be dissolved or desorbed from the membrane. Incompatibility of the copolymer and the polysulfone resin is another problem which limits the composition of the solvent used for preparing the mixed solution.
Japanese Patent Application Laid-open No. H05-177119 discloses a membrane produced by coating the surface of a porous membrane made from polyolefin or polyolefin fluoride with a copolymer of 2-methacryloyloxyethyl phosphorylcholine and methacrylate. However, a large amount of the copolymer, for example, an amount equivalent to 30% or more, preferably 50% or more, of the pore surface of the porous membrane possessing 20 vol % or more void ratio, must be covered to obtain a sufficient effect. This causes the copolymer of 2-methacryloyloxyethyl phosphorylcholine and methacrylate to be also coated over the pore surface inside the hollow fiber membrane, precluding the thick membrane areas from exhibiting hydrophobicity. In addition, the copolymer may be dissolved or desorbed from the membrane.
More recently, diversified and sophisticated functions have been demanded of membranes. In the field of artificial dialysis, for example, countercurrent invasion of endotoxin from the dialysis fluid side caused by high performance membranes has been pointed out. To overcome this problem, development of a high performance membrane capable of eliminating endotoxin and exhibiting no interaction with blood components is desired.